The synthesis and activity evaluation of N-acylated analogs of echinocandin B with improved solubility and lower toxicity.,Journal of Peptide Science

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The synthesis and activity evaluation of N-acylated analogs of echinocandin B with improved solubility and lower toxicity.
Journal of Peptide Science ( IF 1.8 ) Pub Date : 2020-08-03 , DOI: 10.1002/psc.3278
Bing Zhu ₁ , Yuanzhen Dong ₂ , Jie Ma ₂ , Minwei Chen ₂ , Sida Ruan ₃ , Wenjie Zhao ₃ , Jun Feng _{2,

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Affiliation

Presently, echinocandins have been recommended as the first‐line drugs for the treatment of invasive candidiasis. However, low oral bioavailability and solubility limit their application. To improve this situation, this study chose amino acid and fatty acid as raw materials to modify the nucleus of echinocandin B. Six N‐acylated analogs were screened from the derivatives that possessed potent antifungal activity and good water solubility. Based on antifungal susceptibility and hemolytic toxicity, compound 5 as the candidate had good antifungal activity and no hemolytic effect. Moreover, compared with anidulafungin, compound 5 showed a comparable fungicidal effect, much higher solubility, and lower toxicity. In conclusion, compound 5 has the potential for further research and development on account of reserved antifungal activity, high solubility, and low toxicity.

中文翻译：

棘皮菌素B的N-酰化类似物的合成和活性评估具有改善的溶解度和较低的毒性。

目前，棘孢菌素被推荐作为治疗浸润性念珠菌病的一线药物。但是，低的口服生物利用度和溶解度限制了它们的应用。为了改善这种情况，本研究选择氨基酸和脂肪酸为原料来修饰棘皮菌素B的核。从具有强大的抗真菌活性和良好水溶性的衍生物中筛选出六个N-酰化的类似物。基于抗真菌药性和溶血毒性，候选化合物5具有良好的抗真菌活性且无溶血作用。而且，与阿尼芬净相比，化合物5显示出可比的杀真菌效果，更高的溶解度和更低的毒性。总之，化合物5 由于保留的抗真菌活性，高溶解度和低毒性，具有进一步研究和开发的潜力。

更新日期：2020-10-02

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